Ipsen and its partner Exelixis announce independent radiology committee review confirms results from Phase 2 CABOSUN trial of cabozantinib versus sunitinib in previously untreated advanced renal cell carcinoma

IRC confirms cabozantinib significantly improved progression-free
survival compared to sunitinib

E.U. regulatory submission remains on track for Q3 2017

PARIS–(BUSINESS WIRE)–Regulatory News:

Ipsen (Euronext: IPN; ADR: IPSEY) and its partner Exelixis (NASDAQ:EXEL)
today announced that the analysis of the review by a blinded independent
radiology review committee (IRC) has confirmed the primary efficacy
endpoint results of investigator-assessed progression-free survival
(PFS) from the CABOSUN randomized Phase 2 trial of cabozantinib as
compared with sunitinib in patients with previously untreated advanced
renal cell carcinoma (RCC) with intermediate- or poor-risk disease per
the International Metastatic Renal Cell Carcinoma Database Consortium
(IMDC). Per the IRC analysis, cabozantinib demonstrated a clinically
meaningful and statistically significant reduction in the rate of
disease progression or death as measured by PFS. Ipsen remains on track
to submit the regulatory dossier for cabozantinib as a treatment for
first-line advanced renal cell carcinoma in Europe in the third quarter
of 2017.

CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as
part of Exelixis’ agreement with the National Cancer Institute’s Cancer
Therapy Evaluation Program (NCI-CTEP). Exelixis and the Alliance
cooperative group plan to submit these results for presentation at an
upcoming international medical meeting.

David Meek, Ipsen’s Chief Executive Officer stated: “Following
the European commission approval of cabozantinib in second line advanced
RCC, cabozantinib has demonstrated clinical benefit in patients with
advanced RCC in the first-line setting. With our partner Exelixis, we
are very pleased that CABOSUN’s primary endpoint of a statistically
significant improvement of progression-free survival has been confirmed
by the independent radiology review committee in patients with
previously untreated advanced intermediate- or poor-risk RCC. We intend
to file these important data with European regulatory authorities in the
third quarter of 2017.”

About the CABOSUN Study

On May 23, 2016, Exelixis announced that CABOSUN met its primary
endpoint, demonstrating a statistically significant and clinically
meaningful improvement in PFS compared with sunitinib in patients with
advanced intermediate- or poor-risk RCC as determined by investigator
assessment. CABOSUN was conducted by The Alliance for Clinical Trials in
Oncology as part of Exelixis’ collaboration with the NCI-CTEP. These
results were first presented by Dr. Toni Choueiri at the meeting of the
European Society for Medical Oncology (ESMO) 2016, and published in the
Journal of Clinical Oncology (Choueiri, JCO, 2016).
1

CABOSUN was a randomized, open-label, active-controlled phase 2 trial
that enrolled 157 patients with advanced RCC determined to be
intermediate- or poor-risk by the IMDC criteria. Patients were
randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib
(50 mg once daily, four weeks on followed by two weeks off). The primary
endpoint was PFS. Secondary endpoints included overall survival and
objective response rate. Eligible patients were required to have locally
advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and
had to be intermediate or poor risk per the IMDC criteria (Heng, JCO,
2009).
2 Prior systemic treatment for RCC was
not permitted.

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2017 statistics cite kidney cancer as
among the top ten most commonly diagnosed forms of cancer among both men
and women in the U.S.
3 Clear cell RCC is the
most common type of kidney cancer in adults.
4
If detected in its early stages, the five-year survival rate for RCC is
high; for patients with advanced or late-stage metastatic RCC, however,
the five-year survival rate is only 12 percent, with no identified cure
for the disease.
5 Approximately 30,000 patients
in the U.S. and 68,000 globally require treatment.
6

The majority of clear cell RCC tumors have lower than normal levels
of a protein called von Hippel-Lindau, which leads to higher levels of
MET, AXL and VEGF.
7,8
These proteins promote tumor angiogenesis (blood vessel growth), growth,
invasiveness and metastasis.
9-12 MET and AXL
may provide escape pathways that drive resistance to VEGF receptor
inhibitors.
8,9

About CABOMETYX™ (cabozantinib)

CABOMETYX is the tablet formulation of cabozantinib. Its targets
include MET, AXL and VEGFR-1, -2 and -3. In preclinical models,
cabozantinib has been shown to inhibit the activity of these receptors,
which are involved in normal cellular function and pathologic processes
such as tumor angiogenesis, invasiveness, metastasis and drug
resistance. CABOMETYX is available in 20 mg, 40 mg or 60 mg doses. The
recommended dose is 60 mg orally, once daily.

On April 25, 2016, the FDA approved CABOMETYX tablets for the
treatment of patients with advanced renal cell carcinoma who have
received prior anti-angiogenic therapy. On September 9, 2016, the
European Commission approved CABOMETYX tablets for the treatment of
advanced renal cell carcinoma in adults who have received prior vascular
endothelial growth factor (VEGF)-targeted therapy in the European Union,
Norway and Iceland.

About Ipsen

Ipsen is a global specialty-driven pharmaceutical group with total
sales close to €1.6 billion in 2016. Ipsen sells more than 20 drugs in
more than 115 countries, with a direct commercial presence in more than
30 countries. Ipsen’s ambition is to become a leader in specialty
healthcare solutions for targeted debilitating diseases. Its fields of
expertise cover oncology, neurosciences and endocrinology (adult &
pediatric). Ipsen’s commitment to oncology is exemplified through its
growing portfolio of key therapies improving the care of patients
suffering from prostate cancer, neuroendocrine tumors, renal cell
carcinoma and pancreatic cancer. Ipsen also has a significant presence
in primary care. Moreover, the Group has an active policy of
partnerships. Ipsen’s R&D is focused on its innovative and
differentiated technological platforms, peptides and toxins, located in
the heart of the leading biotechnological and life sciences hubs (Les
Ulis/Paris-Saclay, France; Slough/Oxford, UK; Cambridge, US). In 2016,
R&D expenditures exceeded €200 million. The Group has more than 4,900
employees worldwide. Ipsen’s shares are traded on segment A of Euronext
Paris (stock code: IPN, ISIN code: FR0010259150) and are eligible to the
“Service de Règlement Différé” (“SRD”). The Group is part of the SBF 120
index. Ipsen has implemented a Sponsored Level I American Depositary
Receipt (ADR) program, which trades on the over-the-counter market in
the United States under the symbol IPSEY. For more information on Ipsen,
visit
www.ipsen.com

Ipsen Forward Looking Statement

The forward-looking statements, objectives and targets contained
herein are based on the Group’s management strategy, current views and
assumptions. Such statements involve known and unknown risks and
uncertainties that may cause actual results, performance or events to
differ materially from those anticipated herein. All of the above risks
could affect the Group’s future ability to achieve its financial
targets, which were set assuming reasonable macroeconomic conditions
based on the information available today. Use of the words “believes,”
“anticipates” and “expects” and similar expressions are intended to
identify forward-looking statements, including the Group’s expectations
regarding future events, including regulatory filings and
determinations. Moreover, the targets described in this document were
prepared without taking into account external growth assumptions and
potential future acquisitions, which may alter these parameters. These
objectives are based on data and assumptions regarded as reasonable by
the Group. These targets depend on conditions or facts likely to happen
in the future, and not exclusively on historical data. Actual results
may depart significantly from these targets given the occurrence of
certain risks and uncertainties, notably the fact that a promising
product in early development phase or clinical trial may end up never
being launched on the market or reaching its commercial targets, notably
for regulatory or competition reasons. The Group must face or might face
competition from generic products that might translate into a loss of
market share. Furthermore, the Research and Development process involves
several stages each of which involves the substantial risk that the
Group may fail to achieve its objectives and be forced to abandon its
efforts with regards to a product in which it has invested significant
sums. Therefore, the Group cannot be certain that favourable results
obtained during pre-clinical trials will be confirmed subsequently
during clinical trials, or that the results of clinical trials will be
sufficient to demonstrate the safe and effective nature of the product
concerned. There can be no guarantees a product will receive the
necessary regulatory approvals or that the product will prove to be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements. Other risks and
uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including interest
rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and health care legislation; global
trends toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent in new
product development, including obtaining regulatory approval; the
Group’s ability to accurately predict future market conditions;
manufacturing difficulties or delays; financial instability of
international economies and sovereign risk; dependence on the
effectiveness of the Group’s patents and other protections for
innovative products; and the exposure to litigation, including patent
litigation, and/or regulatory actions. The Group also depends on third
parties to develop and market some of its products which could
potentially generate substantial royalties; these partners could behave
in such ways which could cause damage to the Group’s activities and
financial results. The Group cannot be certain that its partners will
fulfil their obligations. It might be unable to obtain any benefit from
those agreements. A default by any of the Group’s partners could
generate lower revenues than expected. Such situations could have a
negative impact on the Group’s business, financial position or
performance. The Group expressly disclaims any obligation or undertaking
to update or revise any forward looking statements, targets or estimates
contained in this press release to reflect any change in events,
conditions, assumptions or circumstances on which any such statements
are based, unless so required by applicable law. The Group’s business is
subject to the risk factors outlined in its registration documents filed
with the French Autorité des Marchés Financiers.

The risks and uncertainties set out are not exhaustive and the reader
is advised to refer to the Group’s 2016 Registration Document available
on its website (
www.ipsen.com).

# # #

References

1Choueiri, T.K., et al. Cabozantinib Versus Sunitinib As
Initial Targeted Therapy for Patients With Metastatic Renal Cell
Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN
Trial. Journal of Clinical Oncology. 2016; 35:6, 591-597.

2Heng D.Y., Xie W., Regan M.M., et al. Prognostic factors
for overall survival in patients with metastatic renal cell carcinoma
treated with vascular endothelial growth factor-targeted agents: Results
from a large, multicenter study. Journal of Clinical Oncology. 2009;
27:5794-5799.

3American Cancer Society. Cancer Facts & Figures 2017.
Atlanta: American Cancer Society; 2017.

4Jonasch E., Gao J., Rathmell W.K., Renal cell carcinoma.
BMJ. 2014; 349:g4797.

5Ko, J. J., Choueiri, T.K., et al. First-, second-
third-line therapy for mRCC: benchmarks for trial design from the IMDC.
British Journal of Cancer. 2014; 110: 1917-1922.

6Decision Resources Report: Renal Cell Carcinoma. October
2014 (internal data on file).

7Harshman, L.C. and Choueiri, T.K., Targeting the
hepatocyte growth factor/c-Met signaling pathway in renal cell
carcinoma. Cancer J. 2013; 19(4):316-23.

8Rankin et al., Direct regulation of GAS6/AXL signaling
by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci
U S A. 2014; 111(37):13373-8.
9 Zhou L, Liu X-D,
Sun M, et al. Targeting MET and AXL overcomes resistance to sunitinib
therapy in renal cell carcinoma. Oncogene. 2016;35(21):2687–2697.

10 Koochekpour et al.,The von Hippel-Lindau tumor
suppressor gene inhibits hepatocyte growth factor/scatter factor-induced
invasion and branching morphogenesis in renal carcinoma cells. Mol Cell
Biol. 1999; 19(9):5902–5912.

11. Takahashi A, Sasaki H, Kim SJ, et al. Markedly
increased amounts of messenger RNAs for vascular endothelial growth
factor and placenta growth factor in renal cell carcinoma associated
with angiogenesis. Cancer Res.1994;54:4233-4237.

12. Nakagawa M, Emoto A, Hanada T, Nasu N, Nomura
Y. Tubulogenesis by microvascular endothelial cells is mediated by
vascular endothelial growth factor (VEGF) in renal cell carcinoma. Br J
Urol. 1997;79:681-687

Contacts

For further information:
Ipsen
Media
Didier
Véron, +33 (0)1 58 33 51 16

Senior Vice-President, Public
Affairs and Communication

didier.veron@ipsen.com
or
Brigitte
Le Guennec, +33 (0)1 58 33 51 17

Corporate External
Communication Manager

brigitte.le.guennec@ipsen.com
or
Financial
Community

Eugenia Litz, +44 (0) 1753 627721
Vice-President
Investor Relations

eugenia.litz@ipsen.com
or
Côme
de La Tour du Pin, +33 (0)1 58 33 53 31

Investor Relations
Executive

come.de.la.tour.du.pin@ipsen.com